Non-Coding Variants in and Genes: Potential Impact on Breast and Ovarian Cancer Predisposition

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2018 Nov 21

PMID 30453575

Citations 10

Authors

Elizabeth Santana Dos Santos

Francois Lallemand

Leslie Burke

Dominique Stoppa-Lyonnet

Melissa Brown

Sandrine M Caputo

Etienne Rouleau

Affiliations

Soon will be listed here.

Abstract

and are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to / exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of and are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of genes and their role on breast and ovarian cancer predisposition.

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